In vitro and in vivo evaluation of levofloxacin-eluting hydrogels for the treatment of Pseudomonas bacterial keratitis

Abstract

Purpose : Pseudomonas aeruginosa is the main causative agent of bacterial keratitis and treatment is usually by multiple drug instillations of conventional eye drops. Repeated administration of eye drops may increase drug drainage into the systemic circulation, discourage strict adherence to therapy and result in poor prognosis. The effectiveness of sustained release levofloxacin-eluting hydrogel lenses (LVF) in the treatment of bacterial keratitis was compared to conventional eye drops (CEDs) in in vitro and in vivo models.

Methods : Levofloxacin was loaded into two silicone hydrogel contact lenses (narafilcon A and senofilcon A) by soaking method. Swelling studies, drug release kinetics and clarity were investigated using UV/Vis spectrophotometry. Drug release was fitted to zero order, first order and Higuchi diffusion models to determine the best fitting kinetic model with the highest correlation coefficient. The effectiveness of the modified lenses in comparison to conventional eye drops was investigated in vitro by Kirby Bauer disk diffusion method and in vivo using New Zealand White Rabbits. The rabbits were randomly placed into three treatment groups and one control group. The effectiveness of infection and treatment were confirmed by visual observance, microbial culture test, gram-staining and histology test.

Results : The senofilcon A LVF released approximately 80% of the drug in 45 mins while just about 30% of the drug was released at the same time by narafilcon A lens. The transmissibility of both lenses after modification were above 90% and drug release was shown to be by Fickian diffusion with KorseMeyer Peppas n-value of 0.34 (R² = 0.997) and Higuchi release with R-squared value of 0.991. Swelling studies showed 35% swelling which confirms good oxygen permeability despite the modification. LVF narafilcon A lens and 5% levofloxacin eye drop showed susceptibility against Pseudomonas aeruginosa with inhibition zones of 34.0 ± 1.41 and 28.3 ± 0.58 mm respectively. Gram staining method confirmed the presence of gram-negative bacteria and subculturing of eye swabs on cetrimide agar confirmed elimination of Pseudomonas infection on day 7 of treatment with LVF and CEDs.

Conclusions : Once daily replacement of levofloxacin-eluting contact lens is comparable to the multiple instillations of levofloxacin eye drops in the treatment of ocular pseudomonas bacterial infection.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.